Randomized HaploCord Blood Transplantation vs. Double Umbilical Cord Blood Transplantation for Hematologic Malignancies

This is a clinical trial for subjects with hematologic malignancies ( acute myelogenous
leukemia, acute lymphocytic leukemia, Hodgkin's or Non-Hodgkin's lymphoma, or myelodysplastic
syndrome) who are in need of a donor stem cell transplant, and for whom an umbilical cord
blood transplant is thought to be the best option. For allogeneic transplant donors, we
typically try to use related family members, such as brothers or sisters, or volunteer donors
who are 'HLA matched', i.e. share similar proteins on their cells. This study is for subjects
for whom such a matched sibling donor or a matched unrelated donor is not available.

This study tests a new method of bone marrow transplantation called combined haplo-identical
cord (haplo-cord) transplantation. In this procedure, cells from a related donor who shares
half of the HLA proteins ( haplo-identical)are collected from the blood, as well as cells
from an umbilical cord, and then both are transplanted. It is hoped that by using cells from
a haplo-identical relative, subjects will have a faster recovery and require fewer
transfusions. Over time the haplo-identical cells from the relative are replaced by the cells
from the cord blood. The combined transplantation of haplo-identical stem cells and cord
blood has previously been used in approximately 60 subjects with very encouraging results.

The purpose of this study is to compare the efficacy of haplo-cord transplant (
"investigational" arm) with the more commonly used procedure in which only the cells
contained in one or two umbilical cords are infused ("standard" arm). Subjects will be
randomly assigned into either the haplo-cord group or the umbilical cord group.

If randomized to the haplo-cord group, a family member will undergo a stem cell collection.
In both arms, subjects will receive a "conditioning regimen" prior to transplantation. The
conditioning regimen consists of chemotherapy, which is meant to destroy the cancer cells and
suppress the immune system to allow the transplanted cells to grow. Subjects will remain in
the hospital until the stem cells are fully recovered, which is usually 4 to 6 weeks after
the transplant. Subjects will have bone marrow aspiration and biopsy at 3 weeks, 4 weeks, 2
months, 6 months and 1 year after the transplant and then yearly thereafter. Participation in
the study will continue for up to 5 years after transplantation.

Inclusion Criteria:

1. Subject must have a histologically or cytologically confirmed diagnosis of: Acute
Myelogenous Leukemia Myelodysplastic Syndrome Acute Lymphocytic Leukemia Lymphoma
(Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma)

2. Must be > 18 years of age

3. Subject is likely to benefit from allogeneic transplant in the opinion of the
transplant physician

4. An human leukocyte antigen (HLA)-identical related or unrelated donor cannot be
identified within an appropriate time frame

5. Karnofsky Performance Status (KPS) of > 80

6. Subject has acceptable organ and marrow function as defined below: Serum bilirubin <
2.0mg/dL ALT(SGPT) 3 X upper limit of normal Creatinine Clearance > 50 mL/min as
estimated by the modified MDRD equation.18

7. Ability to understand and the willingness to sign a written informed consent document.

8. A preliminary search has identified both:

1. Appropriate umbilical cords for a single, or if necessary a double umbilical cord
blood (UCB) transplant AND

2. An appropriate single UCB as well as an appropriate haplo donor for haplo-cord
transplant

Exclusion Criteria:

1. Myeloproliferative disorders, hemoglobinopathies, severe aplastic anemia or any
diagnosis not listed under 3.1.1

2. Life expectancy is severely limited by concomitant illness or uncontrolled infection

3. Subjects with severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired
pulmonary function tests (PFTs)

4. Subject has evidence of chronic active hepatitis or cirrhosis

5. Subject is HIV-positive

6. Subject is pregnant or lactating. -